Comparing healing effect against ulcerative colitis and toxicological effects of Rosmarinus officinalis: A comprehensive in vivo study of an edible plant in rats
Corresponding Author
Anil Yilmaz
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Trakya University, Edirne, Turkey
Department of Pharmacognosy, Faculty of Pharmacy, Bezmialem Vakif University, Istanbul, Turkey
Correspondence
Anil Yilmaz and Gulacti Topcu, Department of Pharmacognosy, Faculty of Pharmacy, Bezmialem Vakif University, Adnan Menderes Boulevard (Vatan Street), 34093 Fatih, Istanbul, Turkey. Email: [email protected] and [email protected]
Contribution: Conceptualization, Investigation, Methodology, Project administration, Writing - original draft
Search for more papers by this authorFatih Uckaya
Department of Biochemistry, Faculty of Pharmacy, Bezmialem Vakif University, Istanbul, Turkey
Department of Fundamentals of Nursing, Faculty of Health Sciences, Alanya Alaaddin Keykubat University, Antalya, Turkey
Contribution: Conceptualization, Investigation, Methodology, Project administration, Writing - original draft
Search for more papers by this authorNihan Bayindir
Department of Histology, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey
Contribution: Investigation, Methodology
Search for more papers by this authorEray Metin Guler
Department of Biochemistry, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey
Contribution: Investigation, Methodology
Search for more papers by this authorAli Toprak
Department of Biostatistics, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey
Contribution: Investigation, Methodology
Search for more papers by this authorAbdurrahim Kocyigit
Department of Biochemistry, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey
Contribution: Investigation, Methodology, Supervision
Search for more papers by this authorMukaddes Esrefoglu
Department of Histology, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey
Contribution: Investigation, Methodology, Supervision
Search for more papers by this authorCorresponding Author
Gulacti Topcu
Department of Pharmacognosy, Faculty of Pharmacy, Bezmialem Vakif University, Istanbul, Turkey
Correspondence
Anil Yilmaz and Gulacti Topcu, Department of Pharmacognosy, Faculty of Pharmacy, Bezmialem Vakif University, Adnan Menderes Boulevard (Vatan Street), 34093 Fatih, Istanbul, Turkey. Email: [email protected] and [email protected]
Contribution: Conceptualization, Methodology, Project administration, Supervision, Writing - review & editing
Search for more papers by this authorCorresponding Author
Anil Yilmaz
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Trakya University, Edirne, Turkey
Department of Pharmacognosy, Faculty of Pharmacy, Bezmialem Vakif University, Istanbul, Turkey
Correspondence
Anil Yilmaz and Gulacti Topcu, Department of Pharmacognosy, Faculty of Pharmacy, Bezmialem Vakif University, Adnan Menderes Boulevard (Vatan Street), 34093 Fatih, Istanbul, Turkey. Email: [email protected] and [email protected]
Contribution: Conceptualization, Investigation, Methodology, Project administration, Writing - original draft
Search for more papers by this authorFatih Uckaya
Department of Biochemistry, Faculty of Pharmacy, Bezmialem Vakif University, Istanbul, Turkey
Department of Fundamentals of Nursing, Faculty of Health Sciences, Alanya Alaaddin Keykubat University, Antalya, Turkey
Contribution: Conceptualization, Investigation, Methodology, Project administration, Writing - original draft
Search for more papers by this authorNihan Bayindir
Department of Histology, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey
Contribution: Investigation, Methodology
Search for more papers by this authorEray Metin Guler
Department of Biochemistry, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey
Contribution: Investigation, Methodology
Search for more papers by this authorAli Toprak
Department of Biostatistics, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey
Contribution: Investigation, Methodology
Search for more papers by this authorAbdurrahim Kocyigit
Department of Biochemistry, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey
Contribution: Investigation, Methodology, Supervision
Search for more papers by this authorMukaddes Esrefoglu
Department of Histology, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey
Contribution: Investigation, Methodology, Supervision
Search for more papers by this authorCorresponding Author
Gulacti Topcu
Department of Pharmacognosy, Faculty of Pharmacy, Bezmialem Vakif University, Istanbul, Turkey
Correspondence
Anil Yilmaz and Gulacti Topcu, Department of Pharmacognosy, Faculty of Pharmacy, Bezmialem Vakif University, Adnan Menderes Boulevard (Vatan Street), 34093 Fatih, Istanbul, Turkey. Email: [email protected] and [email protected]
Contribution: Conceptualization, Methodology, Project administration, Supervision, Writing - review & editing
Search for more papers by this authorFunding information
This work was supported by Bezmialem Vakif University, Department of Scientific Research Projects [Project No: 6.2014/28]
Abstract
Ulcerative colitis (UC) is a chronic and inflammatory disorder of the gastrointestinal (GI) tract. UC usually worsens the daily life of the patient and may sometimes become mortal. There is no known remedy discovered against UC, yet. Rosmarinus officinalis consists of many flavonoids, phenolics, and terpenoids possessing various biological activities such as anti-inflammatory. For this reason, in the present study, anti-ulcerative colitis effect of ROME (Rosmarinus officinalis methanol extract) was investigated comprehensively by histopathological studies, a number of in vivo anti-inflammatory activities and several in vivo antioxidant activities, in addition to in vitro antioxidant activities and biochemical analyses. In addition, the toxic effects of ROME were examined. The results showed that ROME provided a significant healing effect against ulcerative colitis in rats. Both in vitro and in vivo assay results correlated with histopathological examinations. ROME exhibited minimal toxic alterations. When the results of rosemary are compared with the results of sulfasalazine, it can be suggested that instead of synthetic drugs with side effects, natural sources can be used for the treatment of various diseases. Although some activities of rosemary have been investigated in vitro in the previous studies, this is the first study revealing anti-ulcerative colitis effect of rosemary through histopathological studies, in vivo and in vitro assays as well as biochemical analyses overall.
Practical applications
The results revealed and proved that ROME provided a significant healing effect against ulcerative colitis in rats. When the results of rosemary are compared with the results of sulfasalazine, a commercially available drug on the market, it can be suggested that instead of synthetic drugs with side effects, natural sources can be used for the treatment of various inflammatory diseases such as UC disease. In addition, ROME possesses limited toxic alterations, but not much more than the commercial drug. As a future perspective, lethal and therapeutic doses can be examined and determined. Thus, human studies can be started through this comprehensive in vivo study on rosemary which is commonly used as an edible plant and spice all over the world.
CONFLICT OF INTEREST
The authors declare that they have no competing interests.
Open Research
DATA AVAILABILITY STATEMENT
Not applicable.
REFERENCES
- Abdel-Wahhab, K. G. E.-D., El-Shamy, K. A., El-Beih, N. A. E.-Z., Morcy, F. A., & Mannaa, F. A. E. (2011). Protective effect of a natural herb (Rosmarinus officinalis) against hepatotoxicity in male albino rats. Comunicata Scientiae, 2(1), 9–17. https://doi.org/10.14295/cs.v2i1.82
10.14295/cs.v2i1.82 Google Scholar
- Aebi, H. (1974). Catalase. In H. U. Bergmeyer (Ed.), Methods of enzymatic analysis (pp. 673–680). Verlag Chemie/Academic Press Inc. https://doi.org/10.1016/b978-0-12-091302-2.50032-3
10.1016/B978-0-12-091302-2.50032-3 Google Scholar
- Ahn, E. K., Jeon, H. J., Lim, E. J., Jung, H. J., & Park, E. H. (2007). Anti-inflammatory and anti-angiogenic activities of Gastrodia elata Blume. Journal of Ethnopharmacology, 110(3), 476–482. https://doi.org/10.1016/j.jep.2006.10.006
- Albuquerque, U. P., Medeiros, P. M., Almeida, A. L. S., Monteiro, J. M., Neto, E. M. F. L., Melo, J. G., & Dos Santos, J. P. (2007). Medicinal plants of the caatinga (semi-arid) vegetation of NE Brazil: A quantitative approach. Journal of Ethnopharmacology, 114(3), 325–354. https://doi.org/10.1016/j.jep.2007.08.017
- Al-Sereiti, M. R., Abu-Amer, K. M., & Sen, P. (1999). Pharmacology of rosemary (Rosmarinus officinalis Linn.) and its therapeutic potentials. Indian Journal of Experimental Biology, 37(2), 124–130.
- Apak, R., Güçlü, K., Ozyürek, M., & Karademir, S. E. (2004). Novel total antioxidant capacity index for dietary polyphenols and vitamins C and E, using their cupric ion reducing capability in the presence of neocuproine: CUPRAC method. Journal of Agricultural and Food Chemistry, 52(26), 7970–7981. https://doi.org/10.1021/jf048741x
- Ayar, B., Sen, A., Topcu, G., & Yilmaz, A. (2016). Evaluation of anti-diabetic potential of circiliol and circilineol using CACO2 cell line. FEBS Journal, 283, 377.
- Bakirel, T., Bakirel, U., Keles, O. U., Ulgen, S. G., & Yardibi, H. (2008). In vivo assessment of antidiabetic and antioxidant activities of rosemary (Rosmarinus officinalis) in alloxan-diabetic rabbits. Journal of Ethnopharmacology, 116(1), 64–73. https://doi.org/10.1016/j.jep.2007.10.039
- Baricevic, D., Sosa, S., Della Loggia, R., Tubaro, A., Simonovska, B., Krasna, A., & Zupancic, A. (2001). Topical anti-inflammatory activity of Salvia officinalis L. leaves: The relevance of ursolic acid. Journal of Ethnopharmacology, 75(2–3), 125–132. https://doi.org/10.1016/s0378-8741(00)00396-2
- Blois, M. S. (1958). Antioxidant determinations by the use of a stable free radical. Nature, 181, 1199–1200.
- Bozin, B., Mimica-Dukic, N., Samojlik, I., & Jovin, E. (2007). Antimicrobial and antioxidant properties of rosemary and sage (Rosmarinus officinalis L. and Salvia officinalis L., Lamiaceae) essential oils. Journal of Agricultural and Food Chemistry, 55(19), 7879–7885. https://doi.org/10.1021/jf0715323
- Cardiff, R. D., Miller, C. H., & Munn, R. J. (2014). Manual hematoxylin and eosin staining of mouse tissue sections. Cold Spring Harbor Protocols, 2014(6), 655–658. https://doi.org/10.1101/pdb.prot073411
- Eckerson, H. W., Wyte, C. M., & La Du, B. N. (1983). The human serum paraoxonase/arylesterase polymorphism. American Journal of Human Genetics, 35(6), 1126–1138.
- Ellman, G. L. (1959). Tissue sulfhydryl groups. Archives of Biochemistry and Biophysics, 82(1), 70–77. https://doi.org/10.1016/0003-9861(59)90090-6
- Erel, O. (2004). A novel automated method to measure total antioxidant response against potent free radical reactions. Clinical Biochemistry, 37(2), 112–119. https://doi.org/10.1016/j.clinbiochem.2003.10.014
- Erel, O. (2005). A new automated colorimetric method for measuring total oxidant status. Clinical Biochemistry, 38(12), 1103–1111. https://doi.org/10.1016/j.clinbiochem.2005.08.008
- Erel, O., & Neselioglu, S. (2014). A novel and automated assay for thiol/disulphide homeostasis. Clinical Biochemistry, 47(18), 326–332. https://doi.org/10.1016/j.clinbiochem.2014.09.026
- Erenmemisoglu, A., Saraymen, R., & Ustun, H. (1997). Effect of Rosmarinus officinalis leaves extract on plasma glucose levels in normoglycaemic and diabetic mice. Pharmazie, 52(8), 645–646.
- Haagen, L., & Brock, A. (1992). A new automated method for phenotyping arylesterase (EC 3.1.1.2) based upon inhibition of enzymatic hydrolysis of 4-nitrophenyl acetate by phenyl acetate. European Journal of Clinical Chemistry and Clinical Biochemistry, 30(7), 391–395. https://doi.org/10.1515/cclm.1992.30.7.391
- Haloui, M., Louedec, L., Michel, J. B., & Lyoussi, B. (2000). Experimental diuretic effects of Rosmarinus officinalis and Centaurium erythraea. Journal of Ethnopharmacology, 71(3), 465–472. https://doi.org/10.1016/s0378-8741(00)00184-7
- Hu, M. L., Louie, S., Cross, C. E., Motchnik, P., & Halliwell, B. (1993). Antioxidant protection against hypochlorous acid in human plasma. The Journal of Laboratory and Clinical Medicine, 121(2), 257–262.
- Huang, S. C., Ho, C. T., Lin-Shiau, S. Y., & Lin, J. K. (2005). Carnosol inhibits the invasion of B16/F10 mouse melanoma cells by suppressing metalloproteinase-9 through down-regulating nuclear factor-kappa B and c-Jun. Biochemical Pharmacology, 69(2), 221–232. https://doi.org/10.1016/j.bcp.2004.09.019
- Jang, S. M., Yee, S. T., Choi, J., Choi, M. S., Do, G. M., Jeon, S. M., Yeo, J., Kim, M. J., Seo, K. I., & Lee, M. K. (2009). Ursolic acid enhances the cellular immune system and pancreatic beta-cell function in streptozotocin-induced diabetic mice fed a high-fat diet. International Immunopharmacology, 9(1), 113–119. https://doi.org/10.1016/j.intimp.2008.10.013
- Kontogianni, V. G., Tomic, G., Nikolic, I., Nerantzaki, A. A., Sayyad, N., Stosic-Grujicic, S., Stojanovic, I., Gerothanassis, I. P., & Tzakos, A. G. (2013). Phytochemical profile of Rosmarinus officinalis and Salvia officinalis extracts and correlation to their antioxidant and anti-proliferative activity. Food Chemistry, 136(1), 120–129. https://doi.org/10.1016/j.foodchem.2012.07.091
- Krawisz, J. E., Sharon, P., & Stenson, W. F. (1984). Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity. Assessment of inflammation in rat and hamster models. Gastroenterology, 87(6), 1344–1350.
- Kültür, S. (2007). Medicinal plants used in Kirklareli Province (Turkey). Journal of Ethnopharmacology, 111(2), 341–364. https://doi.org/10.1016/j.jep.2006.11.035
- Levine, R. L., Garland, D., Oliver, C. N., Amici, A., Climent, I., Lenz, A. G., Ahn, B. W., Shaltiel, S., & Stadtman, E. R. (1990). Determination of carbonyl content in oxidatively modified proteins. Methods in Enzymology, 186, 464–478. https://doi.org/10.1016/0076-6879(90)86141-h
- Lu, J., Zheng, Y. L., Wu, D. M., Luo, L., Sun, D. X., & Shan, Q. (2007). Ursolic acid ameliorates cognition deficits and attenuates oxidative damage in the brain of senescent mice induced by D-galactose. Biochemical Pharmacology, 74(7), 1078–1090. https://doi.org/10.1016/j.bcp.2007.07.007
- Moreno, M. I., Isla, M. I., Sampietro, A. R., & Vattuone, M. A. (2000). Comparison of the free radical-scavenging activity of propolis from several regions of Argentina. Journal of Ethnopharmacology, 71(1–2), 109–114. https://doi.org/10.1016/s0378-8741(99)00189-0
- Neuman, M. G. (2007). Immune dysfunction in inflammatory bowel disease. Translational Research: The Journal of Laboratory and Clinical Medicine, 149(4), 173–186. https://doi.org/10.1016/j.trsl.2006.11.009
- Ohkawa, H., Ohishi, N., & Yagi, K. (1979). Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry, 95(2), 351–358. https://doi.org/10.1016/0003-2697(79)90738-3
- Re, R., Pellegrini, N., Proteggente, A., Pannala, A., Yang, M., & Rice-Evans, C. (1999). Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radical Biology & Medicine, 26(9–10), 1231–1237. https://doi.org/10.1016/s0891-5849(98)00315-3
- Sen, A., Ayar, B., Topcu, G., & Yilmaz, A. (2016). A promising novel antidiabetic compound: Alysine-A. FEBS Journal, 283, 97–98.
- Señoráns, F. J., Ibañez, E., Cavero, S., Tabera, J., & Reglero, G. (2000). Liquid chromatographic-mass spectrometric analysis of supercritical-fluid extracts of rosemary plants. Journal of Chromatography. A, 870(1–2), 491–499. https://doi.org/10.1016/s0021-9673(99)00941-3
- Slinkard, K., & Singleton, V. L. (1977). Total phenol analyses: Automation and comparison with manual methods. American Journal of Enology and Viticulture, 28, 49–55.
- Stocks, J., Offerman, E. L., Modell, C. B., & Dormandy, T. L. (1972). The susceptibility to autoxidation of human red cell lipids in health and disease. British Journal of Haematology, 23(6), 713–724. https://doi.org/10.1111/j.1365-2141.1972.tb03486.x
- Tlilia, N., & Sarikurkcu, C. (2020). Bioactive compounds profile, enzyme inhibitory and antioxidant activities of water extracts from five selected medicinal plants. Industrial Crops and Products, 151, 112448–112455. https://doi.org/10.1016/j.indcrop.2020.112448
- Tsai, S. J., & Yin, M. C. (2008). Antioxidative and anti-inflammatory protection of oleanolic acid and ursolic acid in PC12 cells. Journal of Food Science, 73(7), H174–H178. https://doi.org/10.1111/j.1750-3841.2008.00864.x
- Uckaya, F., Bektay, Y., Yilmaz, A., Bayindir, N., Selek, S., Topcu, G., & Esrefoglu, M. (2015). Therapeutic effects of licorice (Glycyrrhiza glabra) on colitis through its antioxidant properties and biochemical analyses. Anti-Cancer Drugs, 26, E24–E25.
- Xavier, R. J., & Podolsky, D. K. (2007). Unravelling the pathogenesis of inflammatory bowel disease. Nature, 448(7152), 427–434. https://doi.org/10.1038/nature06005
- Yamamoto, J., Yamada, K., Naemura, A., Yamashita, T., & Arai, R. (2005). Testing various herbs for antithrombotic effect. Nutrition, 21(5), 580–587. https://doi.org/10.1016/j.nut.2004.09.016
- Yilmaz, A., Boğa, M., & Topçu, G. (2016). Novel terpenoids with potential anti-Alzheimer activity from nepeta obtusicrena. Records of Natural Products, 10(5), 530–541.
- Yilmaz, A., Çağlar, P., Dirmenci, T., Gören, N., & Topçu, G. (2012). A novel Isopimarane diterpenoid with acetylcholinesterase inhibitory activity from Nepeta sorgerae, an endemic species to the Nemrut Mountain. Natural Product Communications, 7(6), 693–696.
- Yilmaz, A., Crowley, R. S., Sherwood, A. M., & Prisinzano, T. E. (2017). Semisynthesis and kappa-opioid receptor activity of derivatives of Columbin, a Furanolactone diterpene. Journal of Natural Products, 80(7), 2094–2100. https://doi.org/10.1021/acs.jnatprod.7b00327
- Yu, Y. X., Gu, Z. L., Yin, J. L., Chou, W. H., Kwok, C. Y., Qin, Z. H., & Liang, Z. Q. (2010). Ursolic acid induces human hepatoma cell line SMMC-7721 apoptosis via p53-dependent pathway. Chinese Medical Journal, 123(14), 1915–1923.